Detection of a novel mutation in the GAA gene in an Iranian child with glycogen storage disease type II.

Glycogen storage disease II (GSDII or Pompe disease, OMIM # 232300) is an autosomal recessive hereditary lysosomal disorder. Mutations in the GAA gene usually lead to reduced acid α-glucosidase (acid maltase, GAA, OMIM *606800, EC 3.1.26.2) activity, which results in impaired degradation and subsequent accumulation of glycogen within lysosomes. We present an Iranian boy, who was diagnosed with GSDII based upon clinical and biochemical findings. A single adenine insertion (insA) was detected at codon 693 that leads to a predicted premature stop codon at codon 736 in the GAA gene. The parents were heterozygous for the same change. According to the human genome mutation database (www.hgmd.org) and lecture reviews, the detected change is a novel mutation. We suppose that the discovered insertion in the GAA gene might lead to a reduced activity of the gene product. This assumption is in agreement with biochemical and clinical signs in the patient.

A novel COL7A1 gene mutation in an Iranian individual suffering dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa is a heritable skin disorder with dominant and recessive genetic patterns. Numerous studies underline that both forms are caused by mutations of the COL7A1 gene, which encodes collagen type VII. It has been reported that most mutations detected in the recessive disease form are nonsense mutations or small insertions or deletions leading to frameshift and premature translational termination, which tend to produce severe phenotypes. In contrast, missense mutations causing amino acid substitutions, which result in variable phenotypes, predominate in the dominant form of dystrophic epidermolysis bullosa. Genomic DNA from the patient and parents was subjected to PCR amplification of the coding region of the COL7A1 gene. Direct sequencing of the PCR products revealed a homozygous single-base deletion in the patient (c.6269-6270delC). The parents were heterozygous for the same mutation. This deletion is a novel mutation in the human COL7A1 gene based on comparisons with the Human Genome Mutation Database. To our knowledge, this is the first report of dystrophic epidermolysis bullosa in an Iranian patient confirmed by molecular diagnosis.

Absence of mutations in GJB2 (Connexin-26) gene in an ethnic group of southwest Iran.

BACKGROUND: The common GJB2 gene mutation (35delG) has been previously reported from Iranian patients that were affected with nonsyndromic autosomal recessive deafness. We, therefore, for the first time, investigated the prevalence and frequency of the GJB2 gene mutation in the Iranian deaf population with Arabian origins. MATERIALS AND METHODS: We amplified and sequenced the entire coding sequence of the GJB2 gene from 61 deaf patients and 26 control subjects. RESULT: None of the analyzed samples revealed deafness-associated mutation. CONCLUSION: This finding differs from several reports from Iran as we have focused on the GJB2 gene that possesses various mutations as the cause of congenital recessive deafness.

Novel mutation in the EXT-1 gene in an Iranian family affected with hereditary multiple exostoses.

Identification of casual mutations in Hereditary Multiple Exostoses (HME) is important because of similar conditions in which multiple exostoses occur. Therefore mutation analysis can help to confirm the clinical diagnosis and to improve the management of therapy. HME is an inherited disorder of bone growth. HME can be referred to by various names such as Heredity Multiple Exostoses, Hereditary Multiple Osteochondromata, Multiple Carthaginous Exostoses, etc. People who have HME grow exostoses, or bony bumps, on their bones which can vary in size, location and number depending on the individual. HME is inherited in an autosomal dominant manner with an estimated prevalence of 1/50,000 in western countries. At least three loci (EXT1, EXT2 and EXT3) thought to be involved in this skeletal disease. Approximately 90% of affected families possess mutations in the coding regions of EXT1 and EXT2 genes and the majority of these mutations cause loss of function. EXT1 and EXT2 genes encode related members of a putative tumor suppressor family. In this first report from Iran we identified a frame shift mutation (1100-1101 insA) in exon 3 of EXT1 gene in a family being suspicious of HME. This mutation leads to a premature stop codon and previously not described. Additionally, we have found an unreported silent mutation in the exon six of EXT1 gene with uncertain significance.